FIG. 8.

SIRT1 binds and deacetylates the AR. (A) Homology model of AR “KLKK” peptide with NAD bound SIRT1. The structures of the hSirT1 and AR “KLKK” peptide-NAD complex are shown as a ribbon model generated using the molecular display program CHIMERA. The “KLKK” peptide (yellow) and the NAD molecule (cyan) are shown as a “ball-and-stick” model. (B) Schematic representation of AR bound to corepressors in the absence of ligand in the context of local chromatin, dependent in part upon the AR lysine motif. SIRT1 inhibits AR activity. SIRT1 is shown to associate with the NCoR/HDAC repression complex. (C) Upon the addition of ligand (DHT), disengagement of the corepressor complex and recruitment of the coactivator complex engages gene expression, dependent in part upon the AR lysine motif.